OBJECTIVE To investigate the relationship of long non-coding RNA （LncRNA） metastasis-associated lung adenocarcinoma transcript 1 （MALAT1） and doxorubicin （DOX） resistance in osteosarcoma （OS） cells. METHODS MG-63 and MG-63/DOX cells were treated with different concentrations of DOX （0， 0.01， 0.05， 0.1， 1 μmol/L）， and survival rates and half maximal inhibitory concentration were determined using CCK-8 assay. The expressions of LncRNA MALAT1 in MG-63 and MG-63/ DOX cells were detected by real-time quantitative fluorescence PCR. MG-63/DOX cells were divided into Control group， knocking down LncRNA MALAT1 negative control （sh-NC） group， sh-MALAT1 group， sh-MALAT1+anti-NC group， and sh-MALAT1+ anti-miR-154-5p group. The expressions of LncRNA MALAT1， miR-154-5p and cyclin D1 （CCND1） mRNA in MG-63/DOX cells of each group were detected. The effects of knocking down LncRNA MALAT1 on the proliferation， migration， invasion， and apoptosis of MG-63/DOX cells were detected by CCK-8 assay， scratch test， Transwell experiment and flow cytometry， respectively. The expression of proliferating cell nuclear protein （PCNA） and CCND1 protein in MG-63/DOX cells was detected by Western blot assay. Interactions between LncRNA MALAT1 and miR-154-5p， miR-154-5p and CCND1 were detected by dual luciferase reporter gene experiment. RESULTS Compared with 0 μmol/L DOX， 0.01， 0.05， 0.1 and 1 μmol/L DOX could reduce the survival rates of MG-63 and MG-63/DOX cells （except for 0.01 μmol/L DOX） （P＜0.05）， IC50 were 0.07 and 0.13 μmol/L， respectively. The survival rate， cell migration number and invasion number of MG-63/DOX cells， scratch closure rate， mRNA expressions of LncRNA MALAT1， mRNA and protein expressions of CCND1， and PCNA protein expression in sh-MALAT1 group were significantly lower than sh-NC group and Control group； the apoptosis rate and miR-154-5p expression were significantly higher than sh-NC group and Control group （P＜0.05）. sh-MALAT1+anti-miR-154-5p group was able to reverse the aforementioned biological effects in sh-MALAT1 group （P＜0.05）. In MG-63/DOX cells transfected with both MALAT1-wild type （WT） and CCND1-WT， the luciferase activity in the miR-154-5p mimic group was significantly lower than mimic negative control group （P＜ 0.05）. CONCLUSIONS Knocking down LncRNA MALAT1 can inhibit the DOX resistance of OS cells， and its mechanism may be targeting the miR-154-5p/CCND1 axis.

Objective To investigate the effect and mechanism of melatonin on the anoikis of melanoma cells.Methods The drug concentration of melatonin inhibiting melanoma cell line B16-F10 was optimized based on the effect on CCK-8 assay.An anti-anoikis of melanoma cell model was developed and divided it into four groups:The blank control group,the TrkB activator group,the melatonin group and the melatonin+TrkB activator group.Calce-in AM/EthD-1 fluorescence double staining was used to detect the anoikis of melanoma cells.Reactive oxygen spe-cies were detected using the fluorescent probe DCFH-DA.Western blot was used to detect the expression of Nrf2 protein and TrkB protein in each group.Results Melatonin significantly inhibited the proliferation of melanoma cells in a time-and dose-dependent manner with IC50 of 1×10-7 μmol/L.Its inhibitory effect was found to be related to in-duction of anoikis of melanoma cells.Melatonin could upregulate the generation of cellular reactive oxygen species(P<0.05),while addition of TrkB activator antagonized this effect.Melatonin could reduce the expression of Nrf2 protein and TrkB protein in melanoma cells(P<0.05),and the addition of TrkB activator could inhibite the effect of melatonin on the expression of Nrf2 protein and TrkB protein(P<0.05).Conclusions Melatonin can inhibit the pro-liferation of melanoma cell line B16-F10 through the mechanism of inducing anoikis.

Objective To compare the technical indicators and clinical effect of catheter-directed thrombolysis(CDT)via two types of non-popliteal venous access in the treatment of acute mixed-type lower extremity deep vein thrombosis(DVT).Methods The clinical data of 119 patients with acute mixed-type lower extremity DVT,who were admitted to the Affiliated Jiangning Hospital of Nanjing Medical University and the Affiliated Nanjing Hospital of Nanjing Medical University of China to receive CDT treatment from January 2016 to June 2022,were retrospectively analyzed.Of the 119 patients,CDT via deep calf vein access was carries out in 45(calf vein group)and CDT via healthy-side femoral venous access was performed in 74(femoral vein group).The success rate of vascular puncture,success rate of catheterization technique,number of successful CDT venous puncturing,time spent for sheath placement,time spent for catheterization,thrombolysis time,used amount of thrombolytic agent and associated complications(including vein puncturing and anticoagulant thrombolysis-related complications),the thrombolytic effect of different anatomical segments,and the clinical efficacy during the follow-up period for at least 12 months were compared between the two groups.Results Successful catheterization via deep calf vein access and via healthy-side femoral vein access was obtained in 31 and 58 CDT patients respectively,with a technical success rate of 68.89％(31/45)and 78.38％(58/74)respectively,the difference between the two groups was not statistically significant(P=0.248).In 26 patients(67.74％)of the calf vein group,more than two times of puncturing were needed before the sheath placement could be successfully achieved.The time spent for sheath placement in the femoral vein group was(1.84±0.87)min,which was remarkably shorter than(10.52+6.13)min in the calf vein group(P＜0.001),but the time spent for catheterization in the femoral vein group was(41.60±13.31)min,which was obviously longer than(20.06+4.46)min in the calf vein group(P＜0.001).The thrombolysis time in the femoral vein group and the calf vein group was(5.34+1.43)days and(5.06±1.18)days respectively(P=0.354),and the used amount of thrombolytic agent in the femoral vein group was(352.16±71.98)×104 U,which was prominently larger than(284.68±77.64)× 104 U in the calf vein group(P＜0.001).The last follow-up check showed that the patency rate of the popliteal vein in the calf vein group was significantly higher than that in the femoral vein group(P=0.037).No statistically significant differences in the incidence of post-thrombotic syndrome(PTS)and the mean VEINES-QOL/Sym scores existed between the two groups(all P＞0.05).Conclusion Compared with CDT via healthy-side femoral vein access,CDT via deep calf vein access can better remove the thrombus in the popliteal vein and superficial femoral vein,and improve the femoropopliteal vein patency rate,although it has no obvious advantages in reducing the occurrence of PTS and in improving the VEINES-QOL/Sym score,moreover,the deep calf vein puncture and sheath placement require a high-level technique.

Objective:To explore the repair effect of resveratrol combined with Schwann cell-like cells(SCLCs)dif-ferentiated from adipose-derived stem cells(ADSCs)on sciatic nerve injury in rats.Methods:ADSCs were primarily cultured and induced to differentiate into SCLCs.Cell morphology was observed by scanning electron microscopy.West-ern Blot method was used to detect the expressions of S100 calcium-binding protein β(S100β),p75 neurotrophin receptor(p75NTR),and glial fibrillary acidic protein(GFAP).Rats were randomly divided into Control group(Con-trol),Schwann cell-like cell group(SCLCs),resveratrol group(Res),and resveratrol+Schwann cell-like cell group(Res+SCLCs).Eight weeks after the successful establishment of the sciatic nerve injury model,the sciatic nerve func-tion index(SFI)of each group was detected by footprint experiment;the mechanical withdrawal threshold(MWT)was measured by von Frey filament stimulation needle;The wet weight ratio(WR)of the tibialis anterior muscle was deter-mined by weighing method;Western Blot and RT-qPCR methods were used to detect the expressions of neurotrophin-3(NT-3),nerve growth factor(NGF),insulin-like growth factor-1(IGF-1),and brain-derived neurotrophic factor(BDNF)at the injury site.Results:After 8 days of induction of ADSCs,the cells had elongated poles and increased extracellular components;S100β,p75NTR,and GFAP proteins were highly expressed.After treatment with SCLCs,Res,and Res+SCLCs,the SFI and WR of the treatment groups were significantly better than those of the Control group(P＜0.05);the MWT of rats in the Res+SCLCs group and SCLCs group was reduced(P＜0.05).Western Blot re-sults showed that the expressions of NT-3,IGF-1,NGF,and BDNF proteins in rats in the Res+SCLCs group were higher than those in other groups(P＜0.05);The expressions of NT-3,NGF,and BDNF proteins in rats in the SCLCs group were higher than those in the Control group(P＜0.05);the expressions of NT-3 and NGF proteins in rats in the Res group were higher than those in the Control group(P＜0.05).RT-qPCR results showed that the expressions of NT-3,IGF-1,NGF,and BDNF mRNA in rats in the Res+SCLCs group were highly expressed;the expressions of NT-3,IGF-1,NGF,and BDNF mRNA in rats in the SCLCs group were higher than those in the Control group(P＜0.05);The expressions of IGF-1 and NGF mRNA in rats in the Res group were higher than those in the Control group(P＜0.05).Conclusion:Res combined with SCLCs differentiated from ADSCs has a good repair effect on sciatic nerve inju-ry in rats.

Objective To investigate the inhibitory effect and molecular mechanism of Huaier granule on the growth of sorafenib resistant hepatocellular carcinoma (HCC) cells. Methods The gradient concentration of Huaier granule was used to treat HCC cells, and the effect of Huaier granule on the proliferation, migration and invasion of sorafenib resistant HCC cells was analyzed. Bioinformatics methods were used to analyze the possible interaction between microRNA-31-5p (miR-31-5p) and sprouty-related proteins with an EVH1 domain 1 (SPRED1). The expression levels of miR-31-5p and SPRED1 in HCC cells were detected by real time fluorescence quantitative polymerase chain reaction (qRT-PCR); cell viability, proliferation, migration, invasion and apoptosis were detected by CCK-8, colony formation, scratch healing, Transwell and flow cytometry; RNA immunoprecipitation (RIP) assay and dual luciferase assay were used to verify the binding relationship between miR-31-5p and SPRED1. Results Huaier granule could significantly inhibit the proliferation, migration and invasion of sorafenib resistant HCC cells, and induce apoptosis. Bioinformatics analysis showed that miR-31-5p was highly expressed in HCC, and Huaier granule was able to down-regulate the expression of miR-31-5p, inhibit the proliferation and metastasis of sorafenib resistant HCC cells, and induce apoptosis; miR-31-5p showed a targeted inhibition effect on the expression of SPRED1. SPRED1 was down-regulated in HCC, and overexpression of SPRED1 was able to reverse the promoting effect of overexpression of miR-31-5p on proliferation and metastasis of sorafenib resistant HCC. Conclusion Huaier granule can inhibit sorafenib resistant HCC metastasis through the miR-31-5p/SPRED1 axis, indicating that Huaier granule has the potential to be used as a novel drug for HCC treatment.

Background: The Lymphadenectomy in Ovarian Neoplasms (LION) study revealed that systemic lymphadenectomy did not bring survival benefit for advanced ovarian cancer patients with clinically normal lymph nodes and was associated with a higher incidence of operative complications. However, there is no consensus on whether lymphadenectomy has survival benefit or not in early epithelial ovarian cancer (EOC). Methods We designed the LOVE study, a multicenter, randomized controlled, phase III trial to compare the efficacy and safety of comprehensive staging surgery with or without lymphadenectomy in stages IA-IIB EOC and fallopian tube carcinomas (FTC). The hypothesis is that the oncological outcomes provided by comprehensive staging surgery without lymphadenectomy are non-inferior to those of conventional completion staging surgery in early-stage EOC and FTC patients who have indications for post-operative adjuvant chemotherapy. Patients assigned to experimental group will undergo comprehensive staging surgery, but lymphadenectomy. Patients assigned to comparative group will undergo completion staging surgery including systematic pelvic and para-aortic lymphadenectomy. All subjects will receive 3–6 cycles of standard adjuvant chemotherapy. Major inclusion criteria are pathologic confirmed stage IA-IIB EOC or FTC, and patients have indications for adjuvant chemotherapy either confirmed by intraoperative fast frozen section or previous pathology after an incomplete staging surgery. Major exclusion criteria are non-epithelial tumors and low-grade serous carcinoma. Patients with severe rectum involvement which lead to partial rectum resection will be excluded. The sample size is 656 subjects. Primary endpoint is disease-free survival.

Objective     To assess the safety and clinical outcomes of segmentectomy in one- or two-staged video-assisted thoracoscopic surgery (VATS) for bilateral lung cancer. Methods    We retrospectively enrolled 100 patients who underwent VATS segmentectomy for bilateral lung cancer at the Department of Thoracic Surgery of Peking Union Medical College Hospital from December 2013 to May 2022. We divided the patients into two groups: a one-stage group (52 patients), including 17 males and 35 females with a mean age of 55.17±11.09 years, and a two-stage group (48 patients), including 16 males and 32 females with a mean age of 59.88±11.48 years. We analyzed multiple intraoperative variables and postoperative outcomes. Results     All 100 patients successfully completed bilateral VATS, and at least unilateral lung received anatomical segmentectomy. Patients in the one-stage group were younger (P=0.040), had lower rate of comorbidities (P=0.030), were less likely to have a family history of lung cancer (P=0.018), and had a shorter interval between diagnosis and surgery (P=0.000) compared with patients in the two-stage group. Wedge resection on the opposite side was more common in the one-stage group (P=0.000), while lobectomy was more common in the two-stage   group. The time to emerge from anesthesia in the one-stage group was longer than that in the first and second operations of the two-stage group (P=0.000, P=0.002). Duration of surgery and anesthesia were similar between two groups (P>0.05). Total number of lymph node stations for sampling and dissection (P=0.041) and lymph nodes involved (P=0.026) were less in the one-stage group. Intraoperative airway management was similar between two groups (P>0.05). The one-stage group was associated with lower activities of daily living (ADL) scores. Conclusion     Segmentectomy is safe in one- or two-staged VATS for bilateral lung cancer, including contralateral sublobectomy and lobectomy. Duration of surgery and perioperative complications are similar between two groups, but the one-stage group is associated with lower ADL scores. On the basis of comprehensive consideration in psychological factors, physical conditions and personal wishes of patients, one-staged sequential bilateral VATS can be the first choice.

Objective:To investigate the efficacy of bare stent implantation alone and stent assisted coiling in the repair of isolated superior mesenteric artery dissection (ISMAD) false lumen.Methods:Clinical data of 50 patients with ISMAD who underwent endovascular treatment between December 2012 and March 2021 were analyzed retrospectively. Depending on the endoluminal treatment methods, they were divided into the bare stent implantation alone group (29 cases) and the stent assisted coiling group (21 cases), and the rates of complete postoperative dissection remodeling, stent restenosis, and symptom recurrence were compared between the two groups.Results:The rates of complete remodeling of the dissection in the immediate postoperative period, 3 months and 6 months in the bare stent placement alone group were 13.8% (4/29), 51.7% (15/29) and 75.9% (22/29), respectively, which were lower than that of the stent assisted coiling group 71.4% (15/21), 85.7% (18/21), and 100% (21/21), and the difference was statistically significant (χ 2=17.17, 6.27, 4.06 respectively, and P=0.001, 0.012, 0.044 respectively). While the rates of complete remodeling of the dissection were 82.8%(24/29), 100%(21/21) in the two groups at 12 months after surgery, respectively, and the difference was not statistically significant (χ 2=2.34, P=0.126). There was no significant difference in stent patency rate and symptom recurrence rate between the two groups ( P>0.05). Conclusions:The efficacy of bare stent implantation alone and stent assisted coiling in the treatment of ISMAD is definite. Although the rate of complete remodeling of the dissection with bare stent placement alone is low in the short term, the rate of complete remodeling of the dissection with bare stent implantation alone gradually increases with the extension of time, which is worthy of clinical application and promotion.

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